A monoclonal antibody raised against X‐31 influenza virus reacted with the majority of natural H3N2 viruses isolated between 1968 and 1982. A number of variants of X‐31 and of a receptor‐binding mutant of X‐31 were selected by the antibody during virus replication in eggs and MDCK cells. Antibody‐binding assays indicated that the viruses selected were not antigenic variants and analyses using derivatized erythrocytes showed that their receptor‐binding properties differed from those of the parent viruses. The amino acid substitutions in the variants were all located in the vicinity of the receptor‐binding site and the structural consequences are discussed in relation to the three‐dimensional structure of X‐31 HA. In addition all of the variants fused membranes at higher pH than wild‐type virus indicating that structural modifications in the distal globular region of HA influence the low pH‐induced conformational change required for membrane fusion.